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Cell Therapy for Bone Disease: A Review of Current Status

Istituto Nazionale per la Ricerca sul Cancro, Centro Biotecnologie Avanzate and Dipartimento di Oncologia, Biologia e Genetica, Universitá di Genova, Genova, Italy

Key Words. Bone marrow stromal cell • Mesenchymal stem cell • Adult stem cell • Plasticity • Bone • Regenerative medicine • Tissue engineering • Transplantation • Osteogenesis imperfecta

Ranieri Cancedda, M.D., Istituto Nazionale per la Ricerca sul Cancro, Centro Biotecnologie Avanzate, Largo R. Benzi, 10, 16132 Genova, Italy. Telephone: 39-010-5737-391; Fax: 39-010-5737-405; e-mail: cancedda{at}cba.unige.it

Bone marrow is a reservoir of pluripotent stem/progenitor cells for mesenchymal tissues. Upon in vitro expansion, in vivo bone-forming efficiency of bone marrow stromal cells (BMSCs) is dramatically lower in comparison with fresh bone marrow, and their in vitro multidifferentiation potentials are gradually lost. Nevertheless, when BMSCs are isolated and expanded in the presence of fibroblast growth factor 2, the percentage of cells able to differentiate into the osteogenic, chondrogenic, and adipogenic lineages is greater. Osteogenic progenitors are not exclusive to skeletal tissues. We could also think of cells in different adult tissues as potentially capable of following an osteochondrogenic differentiation pathway, but, under normal physiological conditions, they are inhibited in this process by the environment and/or the adjacent cell populations. When, for some reason such as pathology, the environment changes dramatically and the inhibiting condition is removed, these cells could become osteoblasts. Bone is repaired via local delivery of cells within a scaffold. Bone formation was first assessed in small animal models. Large animal models were successively developed to prove the feasibility of the tissue engineering approach in a model closer to a real clinical situation. Eventually, pilot clinical studies were performed. Extremely appealing is the possibility of using mesenchymal progenitors in the therapy of genetic bone diseases via systemic infusion. There is experimental evidence to suggest that mesenchymal progenitors delivered by this route engraft with a very low efficiency and do not produce relevant and durable clinical effects. Under some conditions, where the local microenvironment is either altered (i.e., injury) or under important remodeling processes (i.e., fetal growth), engraftment of stem and progenitor cells seems to be enhanced. A better understanding of their engraftment mechanisms will, hopefully, extend the field of therapeutic applications of mesenchymal progenitors.

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